RESUMEN
Worldwide, medicinal plants have been known for economic and geographical advantages, thus possibly holding potentiality against dengue hemorrhagic fever. The methanol/water extracts from different parts of fourteen Vietnam-based plant species were subjected for experimental screening on anti-dengue activity using baby hamster kidney cells (BHK21) and plaque reduction neutralisation test (PRNT). Firstly, the methanol/water extracts were tested against serotype dengue virus DENV-1. Seven out from nineteen extracts show the PRNT50 values less than 31.25â µg/mL. Four of the above extracts namely from Euphorbia hirta, Cordyline terminalis, Carica papaya, and Elaeagnus latifolia were chosen for testing against the serotype DENV-2. All of them exhibit good activity with the PRNT50 values less than 31.25â µg/ml, which were further fractionated to obtain hexane, ethyl acetate and butanol fractions. Anti-dengue virus activity of the fractions against four serotypes DENV-1, -2, -3 and -4 was evaluated. As results, the ethyl acetate fraction of Elaeagnus latifolia is highly active against all four serotype viruses. The structural formulae of its nine constituents were input for molecular docking simulation. The docking-based order for static inhibitability is 6-3L6P>7-3L6P>9-3L6P>2-3L6P>3-3L6P≈5-3L6P>9-3L6P>1-3L6P>8-3L6P; QSARIS-based analysis reveals the biocompatibility of the most promising ligands (4-7); ADMET-based analysis expects their pharmacological suitability. Exceptional finding on 2-3LKW hydrophilic interaction at Lys43 (with the associated Gibbs free energy of -10.3â kcal mol-1 ) raises an open explanation for inhibitory effects. The results encourage further investigations for more in-depth mechanisms and drug development, such as inâ vitro enzyme assays or inâ vitro clinical trials with natural substances from E.â latifolia.
Asunto(s)
Plantas Medicinales , Antivirales/química , Antivirales/farmacología , Pueblo Asiatico , Humanos , Metanol , Simulación del Acoplamiento Molecular , Plantas Medicinales/química , Vietnam , AguaRESUMEN
Distichochlamys citrea M.F. Newman (commonly known as "Black Ginger") is an endemic plant to Vietnam and has been extensively exploited by folk medication for treatments of infection-related diseases and diabetes. In this work, its rhizomes were subjected to fractionated extraction, phytochemical examination, evaluation of antioxidant effect by DDPH free radical neutralization, and inhibitory activity toward α-glucosidase. The compositional components were subjected to in silico screening, including density functional theory calculation, molecular docking simulation, physicochemical analysis, and pharmacokinetic regression. In the trials, EtOAc fraction is found as the bioactive part of most effectiveness, regarding both antioxidant effect (IC50 = 90.27 µg mL-1) and α-glucosidase inhibitory activity (IC50 = 115.75 µg mL-1). Chemical determination reveals there are 13 components of its composition. DFT-based calculations find no abnormal constraints in their structures. Docking-based simulation provides order of inhibitory effectiveness: 3-P53341 > 12-P53341 > 7-P53341 > 4-P53341 > 11-P53341 > 10-P53341. QSARIS-based investigations implicate their biocompatibility. ADMET-based regressions indicate that all candidates are generally safe for medicinal applications. The findings would contribute to the basis for further studies on the chemical compositions of Distichochlamys citrea and their biological activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02273-2.
RESUMEN
Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, 70% ethanolic extracts of P. pterocarpum leaves (LPP) and stem bark (SPP) were evaluated for their low-density lipoprotein (LDL) oxidation and cytotoxic activity against cancer cell lines. Both LPP and SPP inhibited Cu2+-mediated LDL by increasing the lag time of conjugated diene formation and inhibiting the generation of thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. In cancer cells, LPP and SPP triggered the most potent cytotoxic effects against human leukemia cells, CRF-SBA and HL-60, with half-maximal inhibitory concentration (IC50) values ranging from 118.5 to 157.2 µg/mL. SPP exhibited significant cytotoxicity against MIA PACA2, A549, and KG cell lines with IC50 values of 167.5, 244.1 and 255.0 µg/mL, respectively. Meanwhile, LPP showed cytotoxic activity against KG with an IC50 value of 228.1 µg/mL. SPP mediated cytotoxicity in HL-60 and CCRF-SBA cells through the activation of the apoptosis pathway, including the activation of caspases 3, and 9 and poly (ADP-ribose) polymerase (PARP). These results suggested that SPP may prevent the development and progression of atherosclerosis and leukemia in humans.
Asunto(s)
Antioxidantes/farmacología , Proliferación Celular/efectos de los fármacos , Fabaceae/química , Plantas Medicinales/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Medicina Tradicional , Fitoterapia , Extractos Vegetales/farmacología , VietnamRESUMEN
The addition of chalcone and amine components into indirubin-3'-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e, 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3ß enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3ß with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3ß enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.
Asunto(s)
Diseño de Fármacos , Glucógeno Sintasa Quinasa 3 beta/química , Indoles/química , Oximas/química , Antineoplásicos/farmacología , Dominio Catalítico , Supervivencia Celular , Chalconas/química , Biología Computacional , Cristalografía por Rayos X , Células HEK293 , Células HL-60 , Células Hep G2 , Humanos , Concentración 50 Inhibidora , Ligandos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Simulación del Acoplamiento Molecular , Oximas/farmacología , Unión Proteica , Dominios Proteicos , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Objective: Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3′,5′-monophosphate (cGMP) levels and indirectly caused the male ED. Methods: Separation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1-7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares. Results: From the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD. Conclusion: This is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment
Objetivo: Prismatomeris memecyloides Craib (Rubiaceae) es una planta medicinal utilizada tradicionalmente por las minorías étnicas en Vietnam para el tratamiento de la disfunción eréctil (DE). El objetivo de este estudio fue investigar sus composiciones químicas y realizar un cribado virtual de su posible efecto inhibitorio frente a PDE-5 con niveles reducidos de guanosín-3′,5′-monofosfato cíclico (cGMP) y la causa indirecta de la DE en los varones. Métodos: Se realizó la separación de los componentes naturales en una columna cromatográfica con gel de silicio o materiales de cambio de fase, diluyéndolos con diferentes gradientes de disolventes. Se dilucidaron las estructuras de los componentes aislados sobre la base de los datos espectroscópicos (HR-MS, 1D/2D-NMR). Se realizó el estudio de simulación de acoplamiento del componente (1-7) utilizando el protocolo de cadenas laterales flexibles basado en el algoritmo «Iterated Local Search Global Optimizer» de los parámetros farmacocinéticos AutoDock Vina v.1.1.2., calculándose asímismo la predicción de toxicidad mediante los softwares adecuados. Resultados: A partir de los extractos de metanol de las raíces de P. memecyloides recolectadas en Vietnam se aislaron 7 componentes, incluyendo 4 antraquinonas/un glucósido antraquinona denominado damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3), rubiadín-3-metil éter (4) y 1-O-metilrubiadín 3-O-primeverosida (5) junto con 2 glucósidos iridoides, ácido asperulosídico (6) andaitquisonida A (7). Los resultados de modelación molecular reflejaron que 5 componentes de antraquinona poseen las menores energías de ligamiento a PDE-5. El glucósido antraquinona 1-O-metilrubiadín 3-O-primeverosida (5) inhibió potencialmente PDE-5 de manera similar a las PDE-5Is comerciales sildenafil (SLD) y tadalafil (TLD). Los resultados farmacocinéticos calculados como pIC50, pred, miLogP, TPSA, enzima inhibidora de antraquinona glucósido, 1-O-metilrubiadín 3-O-primoverosida (5), fueron similares e incluso más altos que los de los inhibidores comerciales de PDE-5. Especialmente, la toxicidad predictiva de (5) fue incluso menor que la de SLD y TLD. Conclusión: Este es el primer estudio que encuentra una evidencia con base científica para el uso étnico de Prismatormeris memecyloides como planta medicinal para el tratamiento de la DE. El resultado indica que las antraquinonas (damnacantal (1), lucidín-ω-metil éter (2), 3-metilalizarín (3) y rubiadín-3-metil éter (4)), y en especial el glucósido antraquinona (1-O-metilrubiadín 3-O-primeverosida (5)) son componentes de clase farmacológica novel potencial para el tratamiento de la DE
Asunto(s)
Humanos , Masculino , Disfunción Eréctil/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/farmacocinética , Antraquinonas/farmacocinética , Extractos Vegetales/farmacocinética , Rubiaceae/química , Resultado del TratamientoRESUMEN
OBJECTIVE: Prismatomeris memecyloides Craib (Rubiaceae) is a medicinal plant traditionally used by ethnic minorities in Vietnam for the treatment of erectile dysfunction (ED). The aim of this study was to investigate the chemical compositions and screen in silico its possible inhibitory effect against PDE-5 which reduced cyclic guanosine-3',5'-monophosphate (cGMP) levels and indirectly caused the male ED. METHODS: Separation of natural compounds were carried out on chromatographic column with silica gel or reversed phase materials, eluting with different solvent gradients. The structures of all isolated compounds were elucidated on the basis of spectroscopic data (HR-MS, 1D/2D-NMR). Docking simulation study of compound (1-7) was performed by using flexible side chains protocol based on Iterated Local Search Global Optimizer Algorithm of AutoDock/Vina v.1.1.2. Pharmacokinetic parameters and toxicity prediction were also calculated by appropriate softwares. RESULTS: From the methanol extract of roots of P. memecyloides collected in Vietnam, seven compounds including four anthraquinone/one anthraquinone glycoside namely damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3), rubiadin-3-methyl ether (4), and 1-O-methylrubiadin 3-O-primeveroside (5) along with two iridoid glucosides, asperulosidic acid (6) and aitchisonide A (7) were isolated. The molecular modeling results showed that 5 anthraquinone compounds possess the lowest binding energies to PDE-5. The anthraquinone glucoside 1-O-methylrubiadin 3-O-primeveroside (5) potentially inhibited PDE-5 similarly to commercial PDE-5Is sildenafil (SLD) and tadalafil (TLD). Calculated pharmacokinetic results like pIC50,pred; miLogP, TPSA, enzyme inhibitory of anthraquinone glucoside (5) were similar and even higher to those of the commercial PDE-5 inhibitors. Especially the predictive toxicity of 1-O-methylrubiadin 3-O-primeveroside (5) was even lower than those of SLD and TLD. CONCLUSION: This is the first study to find a scientific-based evidence for the ethnic use of P. memecyloides as medicinal plant for the treatment of ED. The result indicates that the anthraquinones (damnacanthal (1), lucidin-ω-methyl ether (2), 3-methylalizarin (3) and rubiadin-3-methyl ether (4)), especially anthraquinone glycoside (1-O-methylrubiadin 3-O-primeveroside (5)) are compounds of potential novel drug class for the ED treatment.
Asunto(s)
Antraquinonas/farmacología , Inhibidores de Fosfodiesterasa 5/farmacología , Extractos Vegetales/farmacología , Rubiaceae/química , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Simulación por Computador , Espectroscopía de Resonancia Magnética/métodos , Medicina Tradicional de Asia Oriental , Simulación del Acoplamiento Molecular , Inhibidores de Fosfodiesterasa 5/química , Inhibidores de Fosfodiesterasa 5/aislamiento & purificación , Extractos Vegetales/química , Raíces de Plantas , VietnamRESUMEN
Two new naphthalene glycosides, morinlongosides A and B (1, 2) and a new iridoid glycoside, morinlongoside C (3), together with four known ones, geniposidic acid (4), (3R)-3-O-[ß-D-xylopyranosyl-(1â6)-ß-D-glucopyranosyl]-l-octen-3-ol (5), lucidin-3-O-ß-primeveroside (6), and morindone-6-O-ß-gentiobioside (7), were isolated from the roots of Morinda longissima Y. Z. RUAN. The structures of all isolated compounds (1-7) were elucidated on the basis of spectroscopic data (high resolution (HR)-MS, one and two dimensional (1/2D)-NMR).
Asunto(s)
Glicósidos/aislamiento & purificación , Glicósidos Iridoides/química , Glicósidos Iridoides/aislamiento & purificación , Morinda/química , Naftalenos/química , Naftalenos/aislamiento & purificación , Raíces de Plantas/química , Glicósidos/química , Conformación Molecular , EstereoisomerismoRESUMEN
Many natural products have been shown to have an inhibitory effect on nitric oxide (NO), and are used as chemotherapy agents for inflammation disease. The current study was designed to evaluate the anti-inflammatory activity of chemical components from the leaves of Ampelopsis cantoniensis. Sixteen compounds (1-16) were isolated and identified. Phloretin (5) and 5,7,3',5'-tetrahydroxyflavanone (16) inhibited nitric oxide (NO) production with IC50 values of 5.2, and 18.5 µM, respectively. The inhibitory effect of compounds 5 and 16 were accompanied by dose-dependent decreases in LPS-induced nitric oxide synthase (iNOS) in RAW 264.7 cells, respectively. This study investigated the significant anti-inflammatory properties of isolated compounds from the leaves of A. cantoniensis for the first time. The findings demonstrate that A. cantoniensis could be used beneficially in the treatment of inflammation disease.
Asunto(s)
Ampelopsis/química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Animales , Línea Celular , Lipopolisacáridos/farmacología , RatonesRESUMEN
Six new phenolics, scutellariosides A-F (1-3, 5-6, and 8), together with six known compounds (4, 7, 9-12) were isolated from the whole plant of Scutellaria indica (Labiatae). The chemical structures of these compounds were determined by spectroscopic analyses including 2D NMR. Their anti-inflammatory activities were evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Among them, compounds 10-12 had inhibitory effects with IC50 values ranging from 7.2 to 27.8µM. Compound 12 reduced LPS-induced iNOS expression in a dose-dependent manner.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Fenoles/química , Fenoles/farmacología , Scutellaria/química , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Ratones , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/inmunología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/inmunología , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
A new alkenylphenol, bavinol A (1), together with six known compounds (2-7) were isolated from the aerial parts of Piper bavinum (Piperaceae). The chemical structures of these compounds were determined by spectroscopic analyses including 2D NMR spectroscopy. The anti-Alzheimer effects of compounds 1-7 were evaluated from acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. Bavinol A (1), ampelopsin (3), and violanthin (4) exhibited AChE inhibitory activities with IC50 values of 29.80, 59.47 and 79.80 µM. Compound 1 also showed the most potent BChE inhibitory activity with an IC50 value of 19.25 µM.
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Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/aislamiento & purificación , Piper , Componentes Aéreos de las Plantas , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Cytotoxic activity-guided fractionation of Erythrophleum fordii led to the isolation of two new cassaine diterpenoid-diterpenoid amide dimers, erythrophlesins H-I (1, 2). Spectral data indicated that they consist of asymmetrical dimeric structure via an ester bond between two cassaine diterpenoids. MTT assay confirmed that compound 1, erythrophlesin H, had the strongest cytotoxic effect toward the human prostate cancer cell line, PC-3. The molecular mechanism by which this compound induced apoptosis cell in prostate cancer remains unknown. Erythrophlesin H induced apoptosis in a dose-dependent manner. Acridine orange and annexin V-FITC/PI double staining confirmed that erythrophlesin H effectively induces apoptosis in PC-3 cells.
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Alcaloides/química , Amidas/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Fabaceae/química , Neoplasias de la Próstata/tratamiento farmacológico , Abietanos , Amidas/química , Antineoplásicos Fitogénicos/química , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Humanos , Técnicas In Vitro , Masculino , Estructura Molecular , Neoplasias de la Próstata/patología , Espectrometría de Masa por Ionización de Electrospray , Células Tumorales CultivadasRESUMEN
The anti-cholinesterase activity was evaluated of the ethyl acetate fraction of the methanol extract of Myristica fragrans Houtt (Myristicaceae) seeds and of compounds isolated from it by various chromatographic techniques. The chemical structures of the compounds were determined from spectroscopic analyses (NMR data). Thirteen compounds (1-13) were isolated and identified. Compound 8 { [(7S)-8'-(4'-hydroxy-3'-methoxyphenyl)-7-hydroxypropyl]benzene-2,4-diol) showed the most effective activity with an IC50 value of 35.1 microM, followed by compounds 2 [(8R,8'S)-7'-(3',4'-methylenedioxyphenyl)-8,8'-dimethyl-7-(3,4-dihydroxyphenyl)-butane] and 11 (malabaricone C) with IC50 values of 42.1 and 44.0 pM, respectively. This is the first report of significant anticholinesterase properties of M. fragrans seeds. The findings demonstrate that M. fragrans could be used beneficially in the treatment of Alzheimer's disease.
Asunto(s)
Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Myristica/química , Acetilcolinesterasa/metabolismo , Estructura MolecularRESUMEN
A new megastigmane glycoside, galloyl linarionoside A (1), together with 13 known compounds (2-14) were isolated from the aerial parts of Aceriphyllum rossii ENGLER. (Saxifragaceae). The chemical structures of the isolated compounds were established mainly by using nuclear magnetic resonance spectra, mass spectrometry, and modified Mosher's method. Among the isolates, compounds 4, 5, 6 and 7 showed potent inhibitory activity against the lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells with IC50 values of 12.5, 9.5, 10.5 and 9.3 µM, respectively. The anti-inflammatory effect of compound 7 was accompanied by dose-dependent decreases in the production of inducible nitric oxide synthase and cyclooxygenase-2 proteins not in the inhibitor kappa B (IκB)-dependent nuclear factor-kappa B activation.
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Antiinflamatorios/química , Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Óxido Nítrico/inmunología , Componentes Aéreos de las Plantas/química , Saxifragaceae/química , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Proteínas I-kappa B/inmunología , Lipopolisacáridos/inmunología , Ratones , FN-kappa B/inmunología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
Inhibition of cholinesterase has been proposed to be a therapeutic target for the treatment of Alzheimer's diseases. In our preliminary screening study on the acetylcholinesterase (AChE) inhibitory activity, an ethyl acetate soluble fraction of the roots of Harpagophytum procumbens (Pedaliaceae) was found to inhibit AChE activity at the concentration of 100 µg/mL. Ten compounds (1-10) were isolated from the active fraction and evaluated for their inhibitory effect on AChE and butyrylcholinesterase (BChE). Among the isolates, verbascosides (5, 6, and 8) containing a caffeoyl and a 3,4-dihydroxyphenethyl groups in their structures, showed effective AChE inhibitory activity and also possessed BChE inhibitory activity. The findings suggest that verbascoside derivatives may be partially related to the anti-Alzheimer effect of this medicinal plant.
Asunto(s)
Catecoles/aislamiento & purificación , Inhibidores de la Colinesterasa/aislamiento & purificación , Disacáridos/aislamiento & purificación , Descubrimiento de Drogas , Glucósidos/aislamiento & purificación , Harpagophytum/química , Nootrópicos/aislamiento & purificación , Raíces de Plantas/química , Acetatos/química , Acetilcolinesterasa , Butirilcolinesterasa , Catecoles/química , Catecoles/farmacología , Fraccionamiento Químico , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Cromatografía Líquida de Alta Presión , Disacáridos/química , Disacáridos/farmacología , Etnofarmacología , Glucósidos/química , Glucósidos/farmacología , Espectroscopía de Resonancia Magnética , Medicina Tradicional Coreana , Estructura Molecular , Nootrópicos/química , Nootrópicos/farmacología , Concentración Osmolar , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Solventes/químicaRESUMEN
Angiogenesis plays a critical role in embryonic development and various physiological processes. However, excessive angiogenesis is associated with several pathological conditions including cancer. Angiogenesis is closely related to tumor growth, invasion and metastasis, and is considered a prime target for anticancer therapy. In this study, two new mono cassaine diterpenoid amides (1, 5) and four known compounds (2-4, 6) were isolated from the bark of Erythrophleum fordii (Leguminosae). Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. The effects of isolates on endothelial tube formation on Matrigel were investigated. Among them, compound 3 was found to have the most potent inhibitory effect on the capillary-like structure formation of human umbilical vein endothelial cells (HUVECs).
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Alcaloides/farmacología , Inhibidores de la Angiogénesis/farmacología , Diterpenos/farmacología , Fabaceae/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Abietanos , Alcaloides/química , Alcaloides/aislamiento & purificación , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Humanos , Conformación Molecular , Corteza de la Planta/química , Relación Estructura-ActividadRESUMEN
Two new phenolic compounds, caesalpiniaphenols G-H (1 and 2), were isolated from Vietnamese Caesalpinia sappan heartwood. The chemical structures were established mainly by extensive spectroscopic studies and chemical evidence. Compounds 1 and 2 showed potent inhibitory activity against HL-60 cancer cell lines with respective IC50 values of 16.7 and 22.5 µg/mL. Treating HL-60 cells with various concentrations of 1 resulted in growth inhibition and the induction of apoptosis.
Asunto(s)
Caesalpinia/química , Citotoxinas/farmacología , Fenoles/farmacología , Extractos Vegetales/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Humanos , Concentración 50 Inhibidora , VietnamRESUMEN
Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. In the course of screening plants used in natural medicines as arginase II inhibitory activity, a methanol extract of Scutellaria indica showed significant inhibitory effect. Further fractionation and repeated column chromatography led to the isolation of a new flavan-type (1), and seven known compounds (2-8). The chemical structures of isolated compounds were elucidated based on extensive 1D and 2D NMR spectroscopic data. The isolates 1-8 were investigated in vitro for their arginase II inhibitory activity using enzyme solution prepared from kidney of anesthetized C57BL/6 mice. Compounds 3 and 5 significantly inhibited arginase II activity with IC50 values of 25.1 and 11.6 µM, respectively, whereas the other compounds were apparently inactive.
Asunto(s)
Arginasa/antagonistas & inhibidores , Arginasa/metabolismo , Flavonoides/química , Flavonoides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Scutellaria/enzimología , Animales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Flavonoides/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL , Componentes Aéreos de las Plantas , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Elevated plasma cholesterol is a hallmark of numerous cardiovascular diseases that are closely linked to endothelial dysfunction indicating decreased nitric oxide (NO) production in the endothelium. It has been previously demonstrated that piceatannol-3'-O-ß-D-glucopyranoside (PG) inhibits arginase activity and reciprocally regulates NO production. Here, we aimed to ascertain whether PG ameliorates vascular function in wild-type (WT) and atherogenic model mice [apolipoprotein E-null mice (ApoE-/-)] and to investigate the possible underlying mechanism. Preincubation of aortic vessels from WT mice fed a normal diet (ND) with PG attenuated vasoconstriction response to U46619 and phenylephrine (PE), while the vasorelaxant response to acetylcholine (Ach) was markedly enhanced in an endothelium-dependent manner. However, the endothelium-independent NO donor, sodium nitroprusside (SNP), did not change vessel reactivity. In thoracic aorta from ApoE-/- mice, a high-cholesterol diet (HCD) induced an increase in arginase activity, a decrease in NO release and an increase in reactive oxygen species generation that was reversed by treatment with PG. The effect of PG was associated with enhanced stability of the eNOS dimer and was not dependent on the expression levels of arginase II and eNOS proteins, although eNOS expression was increased in ApoE-/- mice fed an HCD. Furthermore, PG treatment attenuated the PE-dependent contractile response, and significantly improved the Ach-dependent vasorelaxation response in aortic rings from ApoE-/- mice fed an HCD. On the other hand, PG incubation neither altered the contractile response to a high K+ solution nor the relaxation response to SNP. When analyzing the L-arginine content using high-performance liquid chromatography, PG incubation increased the intracellular L-arginine concentration. PG administration in the drinking water significantly reduced fatty streak formation in ApoE-/- mice fed an HCD. These data indicate that PG improves the pathophysiology of cholesterol-mediated endothelial dysfunction. Therefore, we conclude that the development of PG as a novel effective therapy for preventing atherosclerotic diseases is warranted.
Asunto(s)
Aorta , Apolipoproteínas E/metabolismo , Arginasa/antagonistas & inhibidores , Dieta Alta en Grasa , Glucósidos/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estilbenos/farmacología , Análisis de Varianza , Animales , Aorta/efectos de los fármacos , Aorta/fisiología , Apolipoproteínas E/genética , Arginasa/metabolismo , Estabilidad de Enzimas/efectos de los fármacos , Masculino , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo III/química , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Placa Aterosclerótica/patología , Vasoconstricción/efectos de los fármacosRESUMEN
Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D(2) (2), butyl lucidenate E(2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC(50) values of 7.4, 6.4, 4.3, 9.4, 9.2 and 4.5 µM, respectively. Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions. Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein.
Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Óxido Nítrico/antagonistas & inhibidores , Reishi/química , Triterpenos/química , Triterpenos/farmacología , Línea Celular Tumoral , Ciclooxigenasa 2/biosíntesis , Ciclooxigenasa 2/metabolismo , Inducción Enzimática/efectos de los fármacos , Cuerpos Fructíferos de los Hongos/química , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Resonancia Magnética Nuclear BiomolecularRESUMEN
Four new phenolic compounds, caesalpiniaphenols A-D (1-4), together with eight known compounds were isolated from Caesalpinia sappan heartwood. The chemical structures were established mainly by NMR, MS, ECD, and Mosher's method. Compounds 4, 5, and 7 showed weak inhibitory activity against the LPS-induced NO production in macrophage RAW264.7 cells with IC(50) values of 12.2, 3.5, and 5.7 µM, respectively.